P1739: HEALTH-RELATED QUALITY OF LIFE IN PATIENTS WITH TRIPLE-CLASS EXPOSED RELAPSED/REFRACTORY MULTIPLE MYELOMA TREATED WITH IBERDOMIDE PLUS DEXAMETHASONE IN A PHASE 1B/2A OPEN-LABEL DOSE ESCALATION STUDY
Authors: N. W. van de Donk, S. Guo, L. Shi, J. Lord-Bessen, D. Tang, L. Karlin, K. Weisel, K. Ramasamy, P. C. Abad, A. Amin, S. Amin, S. Lonial
Journal: HemaSphere (2022)

Background: Patients with relapsed/refractory multiple myeloma (RRMM) who are triple-class exposed (TCE) have limited treatment options and experience poor health-related quality of life (HRQoL). Iberdomide (IBER), a novel cereblon E3 ligase modulator (CELMoD®) compound, has shown an overall response rate of 26% in this population when administered with dexamethasone (DEX) in the open-label, single-arm, phase 1b/2a dose-escalation CC-220-MM-001 clinical trial (NCT02773030). Here, we assess the exploratory endpoint of HRQoL for patients enrolled in this clinical trial. Aims: To assess HRQoL in patients with RRMM who received IBER + DEX in cohorts D and I of the CC-220-MM-001 trial. Methods: In this pooled analysis of cohorts D and I, cohort D patients had RRMM; had received ≥3 prior lines of therapy, including lenalidomide, pomalidomide, a proteasome inhibitor, a glucocorticoid, and an anti-CD38 monoclonal antibody; had experienced disease progression within 60 days of last myeloma therapy; and were triple-class refractory. Patients who had received prior anti-B-cell maturation antigen (BCMA) therapy were excluded from cohort D but included in cohort I. In both cohorts, IBER (1.6 mg) was given orally on days 1–21, in combination with DEX (40 mg; 20 mg if >75 years) on day 1, 8, 15, and 22 of each 28-day cycle. The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30), EORTC QLQ-Multiple Myeloma Module (QLQ-MY20), and EuroQoL 5 dimensions 5 levels (EQ-5D-5L) were administered before treatment, on day 1 of each treatment cycle, and at end of treatment. The HRQoL-evaluable population included all patients who received IBER + DEX and who had evaluable assessments of a given HRQoL measure at baseline (cycle 1 day 1) and at ≥1 post-baseline time point. Minimally important differences were prespecified for each domain to interpret whether a mean within-group change from baseline was meaningful. Overall, least square mean HRQoL score changes from baseline were estimated from a mixed-effects model for repeated measures. Proportions of patients who experienced clinically meaningful HRQoL deterioration and improvement were calculated using prespecified responder definitions. Results: A total of 133 patients received IBER + DEX; 99 patients were included in the QLQ-C30-evaluable population (TCE n=79, TCE + anti-BCMA n=20). Median (range) age was 63 (44–82) years, 57% were male, and 95% had ≥4 prior MM regimens (median 6 prior MM regimens). Completion rates for most time points were ≥70%. Mean HRQoL scores were generally stable over time during treatment in all the HRQoL domains, including fatigue, pain, disease symptoms, and side effects. However, the EORTC QLQ-MY20 body image showed clinically meaningful improvement from baseline (Table). At individual level, most patients (≥60%) experienced either clinically meaningful improvement or no change while on treatment in all domains. Image:Summary/Conclusion: HRQoL scores among IBER + DEX patients in cohorts D and I were generally stable in all domains across 3 HRQoL measures. Most patients experienced either clinically meaningful improvement or no change in each domain. This suggests the IBER + DEX treatment maintained HRQoL in heavily pretreated patients with TCE RRMM, while demonstrating a promising clinical response.